Eric Wallace

Eculizumab-induced reversal of dialysis-dependent kidney failure from C3 glomerulonephritis

C3 glomerulopathy (C3G) is characterized by C3 deposits with minimal immunoglobulin deposition caused by alternative complement pathway dysregulation. Unfortunately, no therapeutic intervention has consistently improved outcomes for patients with C3G. Eculizumab, a monoclonal antibody to C5, is currently the only approved complement-specific agent with some efficacy in the treatment of C3 glomerulonephritis (C3GN). Here, we describe a patient with acute crescentic C3GN with no identified complement mutation or family history of renal disease who required dialysis for 6 months. Five months after initiation of eculizumab, she became dialysis independent, showing improvement is possible after adequate time on eculizumab.

Gastrointestinal involvement in Fabry disease. So important, yet often neglected

Fabry disease is an X‐linked metabolic storage disorder due to the deficiency of lysosomal alpha‐galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms – abdominal pain, nausea, diarrhea and diverticular disease – are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.

Economic evaluation of urgent-start peritoneal dialysis versus urgent-start hemodialysis in the United States.

AbstractPatients presenting late in the course of kidney disease who require urgent initiation of dialysis have traditionally received temporary vascular catheters followed by hemodialysis. Recent changes in Medicare payment policy for dialysis in the USA incentivized the use of peritoneal dialysis (PD). Consequently, the use of more expeditious PD for late-presenting patients (urgent-start PD) has received new attention. Urgent-start PD has been shown to be safe and effective, and offers a mechanism for increasing PD utilization. However, there has been no assessment of the dialysis-related costs over the first 90 days of care.The objective of this study was to characterize the costs associated with urgent-start PD, urgent-start hemodialysis (HD), or a dual approach (urgent-start HD followed by urgent-start PD) over the first 90 days of treatment from a provider perspective.A survey of practitioners from 5 clinics known to use urgent-start PD was conducted to provide inputs for a cost model representing typical patients. Model inputs were obtained from the survey, literature review, and available cost data. Sensitivity analyses were also conducted.The estimated per patient cost over the first 90 days for urgent-start PD was

Dasatinib-induced nephrotic-range proteinuria.

16,398. Dialysis access represented 15% of total costs, dialysis services 48%, and initial hospitalization 37%. For urgent-start HD, total per patient costs were

Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

19,352, and dialysis access accounted for 27%, dialysis services 42%, and initial hospitalization 31%. The estimated cost for dual patients was

Late onset variants in Fabry disease: Results in high risk population screenings in Argentina

19,400.Urgent-start PD may offer a cost saving approach for the initiation of dialysis in eligible patients requiring an urgent-start to dialysis.

CATHETER INSERTION AND PERIOPERATIVE PRACTICES WITHIN THE ISPD NORTH AMERICAN RESEARCH CONSORTIUM

Since the introduction of imatinib, tyrosine kinase inhibition has been a mainstay in the treatment of many malignancies. The number of these medications is growing, as are the number of targeted tyrosine kinases. Off-target effects of these medications can have beneficial or adverse effects on the kidney. The onus of knowing the implications of these medications on kidney function, and appropriate treatment when such adverse effects occur, is on the nephrologist. We present a patient with chronic myelogenous leukemia who developed nephrotic-range proteinuria after initiation on dasatinib therapy that resolved after changing therapy to imatinib. The mechanism of kidney injury caused by dasatinib has not been described previously in the literature. We provide a review of vascular endothelial growth factor and its pharmacologic inhibition as it pertains to kidney pathology and propose possible mechanisms by which dasatinib induces kidney injury.

Home Dialysis Utilization Among Racial and Ethnic Minorities in the United States at the National, Regional, and State Level

Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.

Perspectives from the Kidney Health Initiative on Advancing Technologies to Facilitate Remote Monitoring of Patient Self-Care in RRT

Background Screening for Fabry disease (FD) in high risk populations yields a significant number of individuals with novel, ultra rare genetic variants in the GLA gene, largely without classic manifestations of FD. These variants often have significant residual α-galactosidase A activity. The establishment of the pathogenic character of previously unknown or rare variants is challenging but necessary to guide therapeutic decisions. Objectives To present 2 cases of non-classical presentations of FD with renal involvement as well as to discuss the importance of high risk population screenings for FD. Results Our patients with non-classical variants were diagnosed through FD screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage. Conclusions Screening programs for FD in high risk populations are important as FD is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations.

Remote Patient Management for Home Dialysis Patients

♦ Background: In general, efforts to standardize care based on group consensus practice guidelines have resulted in lower morbidity and mortality. Although there are published guidelines regarding insertion and perioperative management of peritoneal dialysis (PD) catheters, variation in practice patterns between centers may exist. The objective of this study is to understand variation in PD catheter insertion practices in preparation for conducting future studies. ♦ Methods: An electronic survey was developed by the research committee of the International Society for Peritoneal Dialysis – North American Research Consortium (ISPD-NARC) to be completed by physicians and nurses involved in PD programs across North America. It consisted of 45 questions related to 1) organizational characteristics; 2) PD catheter insertion practices; 3) current quality-improvement initiatives; and 4) interest in participation in PD studies. Invitation to participate in the survey was given to nephrologists and nurses in centers across Canada and the United States (US) identified by participation in the inaugural meeting of the ISPD-NARC. Descriptive statistics were applied to analyze the data. ♦ Results: Fifty-one ISPD-NARC sites were identified (45% in Canada and 55% in the US) of which 42 responded (82%). Center size varied significantly, with prevalent PD population ranging from 6 – 300 (median: 60) and incident PD patients in the year prior to survey administration ranging from 3 – 180 (median: 20). The majority of centers placed fewer than 19 PD catheters/year, with a range of 0 – 50. Availability of insertion techniques varied significantly, with 83% of centers employing more than 1 insertion technique. Seventy-one percent performed laparoscopic insertion with advanced techniques (omentectomy, omentopexy, and lysis of adhesions), 62% of sites performed open surgical dissection, 10% performed blind insertion via trocar, and 29% performed blind placement with the Seldinger technique. Use of double-cuff catheters was nearly universal, with a near even distribution of catheters with pre-formed bend versus straight inter-cuff segments. There was also variation in the choice of perioperative antibiotics and perioperative flushing practices. Although 86% of centers had quality-improvement initiatives, there was little consensus as to appropriate targets. ♦ Conclusions: There is marked variability in PD catheter insertion techniques and perioperative management. Large multicenter studies are needed to determine associations between these practices and catheter and patient outcomes. This research could inform future trials and guidelines and improve practice. The ISPD-NARC is a network of PD units that has been formed to conduct multicenter studies in PD.